Renal imaging in 199 Dutch patients with Birt-Hogg-Dubé syndrome: Screening compliance and outcome

Abstract

Birt-Hogg-Dubé syndrome is associated with an increased risk for renal cell carcinoma. Surveillance is recommended, but the optimal imaging method and screening interval remain to be defined. The main aim of our study was to evaluate the outcomes of RCC surveillance to get insight in the safety of annual US in these patients. Surveillance data and medical records of 199 patients with Birt-Hogg-Dubé syndrome were collected retrospectively using medical files and a questionnaire. These patients were diagnosed in two Dutch hospitals and data were collected until June 2014. A first screening for renal cell carcinoma was performed in 172/199 patients (86%). Follow-up data were available from 121 patients. The mean follow-up period per patient was 4.2 years. Of the patients known to be under surveillance, 83% was screened at least annually and 94% at least every two years. Thirty-eight renal cell carcinomas had occurred in 23 patients. The mean age at diagnosis of the first tumour was 51. Eighteen tumours were visualized by ultrasound. Nine small tumours (7–27 mm) were visible on MRI or CT and not detected using ultrasound. Our data indicate that compliance to renal screening is relatively high. Furthermore, ultrasound might be a sensitive, cheap and widely available alternative for MRI or part of the MRIs for detecting clinically relevant renal tumours in BHD patients,but the limitations should be considered carefully. Data from larger cohorts are necessary to confirm these observations.

Birt–Hogg–Dubé syndrome

“…In a French series, four patients had metastatic tumours at the time of initial diagnosis or later. The course of the metastatic disease was quite indolent in all patients [80,109].…”

“…The sensitivity of various imaging modalities has been tested in a retrospective Dutch study [109]. Among 199 patients diagnosed with BHD, 172 (86%) patients had an initial renal screen.…”

Loss of FLCN-FNIP1/2 induces a non-canonical interferon response in human renal tubular epithelial cells

“…The lifetime risk for BHD patients to develop RCC is ~10 times higher than for the unaffected population ( Houweling et al, 2011 ; Pavlovich et al, 2005 ; Toro et al, 2008 ; Zbar et al, 2002 ). BHD patients are predisposed to bilateral and multifocal renal tumors ( Nickerson et al, 2002 ; Schmidt et al, 2005 ; Zbar et al, 2002 ) and dependent on surveillance by renal imaging for early detection and curative treatment prior to metastasis ( Johannesma et al, 2019 ). Loss of heterozygosity, by gene silencing or an inactivating somatic mutation of the wild-type FLCN allele, is a prerequisite for kidney cancer development in BHD patients ( Vocke et al, 2005 ).…”

Novel Folliculin Gene Mutations in Polish Patients With Birt-hogg-dubé Syndrome

“…The prevalence of speci c organ lesions in BHDS differs in relation to the cohorts previously reported by a dermatologist, nephrologist and pulmonologist [1,7,16,18,30,31].…”

“…Renal tumours occur, usually in the fth decade of life in < 30% of patients, and sometimes this is an isolated presentation of the disease [16][17][18]. Patients with BHDS develop various kinds of renal tumours, often differentiated within the same organ.…”